We have defined propagable, quantifiable differences between normal and rheumatoid synovial cells in tissue culture, and shown them to be at least partly due to an "activator" material, (connective tissue activating peptide, CTAP), present in excess in rheumatoid cells. CTAP causes "activation" in the sense that it increases energy metabolism and markedly stimulates hyaluronic acid synthesis, both characteristic stigmata of chronic rheumatoid synovitis. These actions of CTAP, and its ubiquitous cellular distribution, qualify it for a role as a key regulator of inflammation, controlling progression from the exudative to the reparative phase. Measurements of CTAP in simple inflammation show an early peak of activity, and continued excess of CTAP was shown to produce the biochemical activities characteristic of chronic rheumatoid inflammation. The objectives of this proposal, therefore, are to: 1) better define the chemical nature of CTAP; 2) to explore the range of its biological effects; 3) to study its mechanism of action; 4) to study its tissue localization in rheumatic diseases by immunologic and chemical methods; 5) to study factors controlling its formation, release, and degradation; 6) to study its detailed relationship to inflammation in human diseases and in model systems, and finally to search for novel ways to interdict the chronic inflammatory process by interfering with connective tissue "activation".